The diagnosis of HMGCS2D primarily relies on an HMG-CoA synthase enzyme assay; however, distinguishing between mitochondrial HMG-CoA synthase and cytosolic HMG-CoA synthase in liver homogenates is challenging, limiting the use of this assay [13]. Here, HMGCS2 is linked to 3-hydroxy-3-methylglutaryl-CoA synthase deficiency.